Although it has been known for millennia that many young women who give birth vaginally will suffer from disabling pelvic organ prolapse later in their lifespan, the factors linking these two events remain a mystery. Of the 3 million women who deliver vaginally each year 300,000 or 1 in 10 will later require surgery for pelvic floor dysfunction due to their unique sex-determined role in reproduction. Our discovery of birth-induced levator ani muscle injury and its strong relationship to prolapse has identified a key connection between birth and prolapse. Ignorance of how birth-induced injury occurs and how it produces subsequent prolapse has blocked efforts to improve prevention and treatment. In this application we seek to continue SCOR support for our broadly interdisciplinary sex-differences research group representing 4 schools and 2 institutes. The group has won 10 awards in the last 4 years for our discoveries and now seeks funding to begin to translate these insights into improved prevention at birth and strategies for better treatment. Project I Birth Biomechanics will test hypotheses concerning basic mechanisms of levator ani injury during vaginal birth to identify specific situations that may increase or decrease injury risk. Project II Injury Extensio will determine whether minor clinically insignificant levator injury after first birth extends to a clinically significant tear during second birth. Because a second birth doubles the risk of genital prolapse, this event offers the opportunity of preventing injury and their sequelae later in life. Project III Muscle-Ligament Dynamics will establish the interaction between birth-related levator muscle injury and the properties of the uterovaginal supporting ligaments associated with prolapse. Core A Administrative/Human Subjects integrates and supports the interdisciplinary team and provides project support by recruiting subjects, compiling and analyzing data and protecting subject safety. Core B Biostatistics/Measurements provides statistical and technical support for the projects along with integrated analysis for 2- and 3-dimensional spatial data gathered across projects. It will prepare data for presentation, publication, subject safety analysis and eventually public use. Core C Translation/Mentorshipw\\\ foster insight dissemination and drive investigator development. This SCOR will produce translational insights to reduce the sex-determined consequences women suffer from their unique role in reproduction. It will establish the scientific basis for new strategies to improve treatment, identify important prevention opportunities, and train a new generation of researchers.